The therapeutic potential of α-tocopheryl succinate (a.k.a., vitamin E succinate; VES) in cancer treatment and prevention has been the focus of many recent investigation. See Neuzil et al., Mol Pharmacol 71, 1185-99 (2007) and Wang et al., Mol Nutr Food Res 50, 675-85 (2006). It is noteworthy that VES suppresses in vitro and in vivo tumor cell growth without incurring significant toxicity to normal cells. A growing body of evidence indicates that VES mediates its antitumor effect by perturbing a multitude of signaling pathways governing cancer cell growth, apoptosis, differentiation, angiogenesis, and metastasis. This broad spectrum of action in conjunction with low toxicity underlies the translational potential of VES in cancer treatment or prevention. Of various target mechanisms reported in the literature, the inhibitory effect of VES on cancer cell adhesion is especially noteworthy. Crispen et al., Prostate 67, 582-90 (2007) This is evident by the ability of α-tocopheryloxyacetic acid, a VES derivative with increased metabolic stability, to suppress breast tumor growth and to reduce lung metastasis in animal models. Hahn et al., Cancer Res, 66, 9374-8 (2006).
Substantial evidence indicates that cell adhesion is critical to the development of different aspects of the malignant phenotype of cancer cells, including survival, invasion, metastasis, and drug resistance. Consequently, targeting adhesion or its associated pathways represents a therapeutically relevant strategy to improve the clinical outcome of many solid and hematological malignancies. Although many humanized antibodies against different adhesion molecules have entered human trials, there exist few small-molecule cell adhesion-targeted agents.